Testing a treatment called isoniazid monotherapy to prevent the progression of chronic kidney disease in latent (without any symptoms) tuberculosis in Bangladesh
| ISRCTN | ISRCTN11515835 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11515835 |
- Submission date
- 06/12/2023
- Registration date
- 13/12/2023
- Last edited
- 18/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims
We aim to conduct a clinical study to investigate the potential benefits of treating latent tuberculosis infection (LTBI) in individuals residing in developing countries with a high incidence of both tuberculosis (TB) and LTBI. Specifically, we are interested in understanding whether treating LTBI can have positive effects on the health of patients with chronic kidney disease (CKD). Our study will explore various health aspects, including assessing whether LTBI treatment reduces the risk of developing active TB, enhances muscle strength (indicative of nutritional status), improves the body's response to insulin, and regulates inflammation levels in the body.
Who can participate?
Patients with Latent Tuberculosis Infection (LTBI), and Chronic Kidney Disease (CKD)
What does the study involve?
Patients will be randomly assigned to one of two groups, similar to flipping a coin. One group will receive daily anti-TB drugs (Isoniazid 5mg/kg and Pyridoxine 20mg) for six months, while the other group will receive no treatment.
The study will span three years, with patients seen by study staff every three months during their usual Kidney Foundation clinic visits. Routine blood tests recommended by their clinic doctor will continue, and any special study-related tests will be provided at no cost to the patients.
What are the possible benefits and risks of participating?
As a participant in this research study, patients may not benefit directly; information from this study will help other people with CKD in the future, whether we should treat LTBI. We already know in many developed countries, in accordance with WHO (World Health Organization) guidelines, LTBI is treated with anti-TB drugs.
The Isoniazid and Pyridoxine given in this study rarely cause any serious adverse effects. Uncommon side effects that you might encounter include anorexia, nausea, vomiting, abdominal discomfort, persistent fatigue, or weakness, dark-coloured urine, pale stools, or jaundice. If side effects are severe, especially if there is evidence that the liver function is affected, they will be asked to stop treatment. We will be monitoring their liver and other tests every 3 months. If they become symptomatic while on treatment they will be asked to contact a member of the research study group immediately (details listed below).
Where is the study run from?
Kidney Foundation (Bangladesh)
When is the study starting and how long is it expected to run for?
March 2023 to February 2028
Who is funding the study?
1. Kidney Foundation (Bangladesh)
2. Barts Health NHS Trust (UK)
3. Queen Mary University London (UK)
Who is the main contact?
Dr Tasnuva Sarah Kashem, tasnuva.kashem@gmail.com
Prof Magdi Yaqoob, m.m.yaqoob@qmul.ac.uk
Dr Stanley Fan, s.fan@qmul.ac.uk
Contact information
Public
House 151, Road 4, Niketan A ,Gulshan 1
Dhaka
1212
Bangladesh
 ORCID ID |
0000-0002-3431-9613 |
|---|---|
| Phone | +880 1759198416 |
| tasnuva.kashem@gmail.com |
Principal Investigator
The Royal London Hospital
P O BOX 59
London
E1 1BB
United Kingdom
| Phone | +44 7958231293 |
|---|---|
| m.m.yaqoob@qmul.ac.uk |
Scientific
The Royal London Hospital
P O BOX 59
London
E1 1BB
United Kingdom
| Phone | +44 7981866440 |
|---|---|
| s.fan@qmul.ac.uk |
Study information
| Study design | Single-site open-label randomized clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet. |
| Scientific title | A single centre, open-label, randomised clinical trial evaluating Isoniazid Monotherapy treatment to Prevent Accelerated Chronic kidney disease in latent Tuberculosis in a High Incidence Country. |
| Study acronym | IMPACT-HIC |
| Study objectives | Whether treatment with 6 months’ isoniazid plus pyridoxine have any effect on the rate of change in eGFR of CKD patients (eGFR 20-60) with Latent Tuberculosis Infection (LTBI) |
| Ethics approval(s) |
Approved 21/03/2023, Institutional Ethical Committee, Kidney Foundation Hospital and Research Institute (Plot5/2, Road-1, Mirpur-2, Dhaka, 1216, Bangladesh; +880 2-9024074; rashid@bol-online.com), ref: KFHRI/ECC-002/2023 |
| Health condition(s) or problem(s) studied | Chronic kidney disease with latent tuberculosis infection |
| Intervention | Intervention - IMP with 6 months isoniazid 5mg/kg/day maximum daily dose 300 mg (plus pyridoxine 20 mg) Comparison group – The alternative group will receive no treatment compared with the intervention group as per current practice in Bangladesh. Patients will then be randomized into one of two groups. One group will receive IMP daily, for 6 months while the second group will receive standard care (no specific treatment for LTBI) for 6 months. The randomization envelopes will be grouped into 20 Blocks (10 envelopes within each group). Each group will contain 5 envelopes specifying IMP and 5 no treatment in random order. Each envelope will be identified by the Block number and kit number The study will comprise of four stratified groups of patients: A. Diabetic and No Glomerulonephritis B. Diabetic and Glomerulonephritis C. Non-Diabetic and Glomerulonephritis D. Non-Diabetic and No Glomerulonephritis |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacodynamic |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Isoniazid/pyridoxine |
| Primary outcome measure | Rate of change in renal function assessed by eGFR [ml/min/1.73m²] over 2 years (1.5 years after administration of 6 months of isoniazid therapy 5mg/kg (maximum 300mg) plus pyridoxine 20mg or no treatment. The eGFR will be calculated using the CKD EPI equation using age, sex, and creatinine. This will be evaluated every 3 months as part of standard care at 0, 3, 6, 9, 12, 15,18,21 and 24 months. |
| Secondary outcome measures | 1. Reactivation of TB monthly during the 2 years follow-up period from initiation of trial. If positive: patient will be withdrawn from trial to initiate TB treatment as deemed clinically appropriate (but will continue follow up for endpoints). 2. Survival benefits-mortality measured using Kaplan-Meier estimate at the end of the study. 3. Effect on other parameters of kidney function performed at CKD clinic as standard practice including but exclusively: urinary microalbumin (ACR), 0, 3, 6 and 12 months. 4. The effect of IMP in the inflammatory status assessed by serum CRP and optical density of IGRA at screening then 9 months and 12 months from initiation of therapy 5. Safety endpoints: SAEs, AEs and liver enzymes (SGPT, ALP, Bilirubin) at 0, 3, 6 and 12 months |
| Overall study start date | 21/03/2023 |
| Completion date | 01/02/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 19 Years |
| Upper age limit | 75 Years |
| Sex | Both |
| Target number of participants | 134 |
| Total final enrolment | 134 |
| Key inclusion criteria | 1. Patients (male or female) eGFR 20-60 [ml/min/1.73m²] attending Kidney Foundation Hospital, Bangladesh. 2. Aged 19 to 75 years inclusive 3. Willing to comply with study schedule 4. Interferon-gamma release assay (IGRA) positive |
| Key exclusion criteria | 1. Active TB or previous known treatment of active TB or LTBI 2. Clinically significant history of abnormal physical and/or mental health as judged by the investigator other than conditions related to chronic kidney disease such as history of liver disease, including viral hepatitis, chronic liver disease, harmful alcohol intake. 3. Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug 4. Subject with a known hypersensitivity or contraindication to Isoniazid and Pyridoxine 5. Female participant who is pregnant or lactating during the trial. 6. History of functional kidney transplant 6 months before study entry |
| Date of first enrolment | 01/01/2024 |
| Date of final enrolment | 01/03/2025 |
Locations
Countries of recruitment
- Bangladesh
Study participating centre
Dhaka
1216
Bangladesh
Sponsor information
Research organisation
Plot5/2, Road-1, Mirpur-2
Dhaka
1216
Bangladesh
| Phone | +880 2-9024074 |
|---|---|
| info@kidneyfoundationbd.com | |
| Website | https://kidneyfoundationbd.com/ |
"ROR" |
https://ror.org/03fnc0m43 |
Hospital/treatment centre
The Royal London Hospital
P O BOX 59
London
E1 1BB
England
United Kingdom
| Phone | +44 7526 187 257 |
|---|---|
| hussain.zina@nhs.net |
University/education
Translational Medicine & Therapeutics
William Harvey Research Limited
2nd Floor John Vane Science Centre, Charterhouse Square
London
EC1M 6BQ
England
United Kingdom
| Phone | +44 20 7882 2107 |
|---|---|
| m.m.yaqoob@qmul.ac.uk | |
| Website | http://www.qmul.ac.uk/ |
|
"ROR" |
https://ror.org/026zzn846 |
Funders
Funder type
Research organisation
No information available
Government organisation / Local government
- Alternative name(s)
- Barts Health
- Location
- United Kingdom
Government organisation / Universities (academic only)
- Alternative name(s)
- Queen Mary Uni of London, Queen Mary, Queen Mary and Westfield College, QMUL, QM
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 12/12/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository, Available on request |
| Publication and dissemination plan | Planned publication in high -impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and /or analysed during the current study will be stored in a non-publicly available repository (Kidney Foundation Hospital and Research Institute, Bangladesh's research lab) and are available from the corresponding author on reasonable request tasnuva.kashem@gmail.com |
Editorial Notes
18/03/2025: The target number of participants was changed from 150 to 134. Total final enrolment added.
10/01/2025: The recruitment end date was changed from 01/02/2025 to 01/03/2025.
30/12/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 01/12/2024 to 01/02/2025.
2. The overall study end date was changed from 01/12/2027 to 01/02/2028.
11/12/2023: Trial's existence confirmed by Kidney Foundation Hospital and Research Institute.
